Interleukin-2 PET imaging in patients with metastatic melanoma before and during immune checkpoint inhibitor therapy

• Published in: European journal of nuclear medicine and molecular imaging Vol. 48; no. 13; pp. 4369 - 4376
• Main Authors: van de Donk, Pim P., Wind, Thijs T., Hooiveld-Noeken, Jahlisa S., van der Veen, Elly L., Glaudemans, Andor W. J. M., Diepstra, Arjan, Jalving, Mathilde, de Vries, Elisabeth G. E., de Vries, Erik F. J., Hospers, Geke A. P.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2021; Springer Nature B.V
• Subjects: Bone marrow; Bone tumors; Cardiology; Computed tomography; Cytokines; Fluorine; Fluorine isotopes; Humans; Imaging; Immune Checkpoint Inhibitors; Immune system; Immunotherapy; Inhibitors; Interleukin 2; Interleukin 2 receptors; Interleukin-2 - therapeutic use; Interleukins; Lesions; Lymphocytes; Lymphocytes T; Lymphoid tissue; Medical imaging; Medicine; Medicine & Public Health; Melanoma; Melanoma - diagnostic imaging; Melanoma - drug therapy; Metastases; Metastasis; Nuclear Medicine; Oncology; Oncology – General; Original; Original Article; Orthopedics; Patients; Pilot Projects; Positron emission; Positron emission tomography; Positron Emission Tomography Computed Tomography; Radiology; Side effects; Spleen; Therapy; Tomography; Tomography, X-Ray Computed; Tumor-infiltrating lymphocytes; Interleukin-2; T cells; Positron emission tomography; Immunotherapy; Melanoma
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-021-05407-y

Purpose Immune checkpoint inhibitors can induce a T cell–mediated anti-tumor immune response in patients with melanoma. Visualizing T cell activity using positron emission tomography (PET) might allow early insight into treatment efficacy. Activated tumor–infiltrating T cells express the high-affinity interleukin-2 receptor (IL-2R). Therefore, we performed a pilot study, using fluorine-18-labeled IL-2 ([ 18 F]FB-IL2 PET), to evaluate whether a treatment-induced immune response can be detected. Methods Patients with metastatic melanoma received ~ 200 MBq [ 18 F]FB-IL2 intravenously, followed by a PET/CT scan before and during immune checkpoint inhibitor therapy. [ 18 F]FB-IL2 uptake was measured as standardized uptake value in healthy tissues (SUV mean ) and tumor lesions (SUV max ). Response to therapy was assessed using RECIST v1.1. Archival tumor tissues were used for immunohistochemical analyses of T cell infiltration. Results Baseline [ 18 F]FB-IL2 PET scans were performed in 13 patients. SUV mean at baseline was highest in the kidneys (14.2, IQR: 11.6–18.0) and liver (10.6, IQR: 8.6–13.4). In lymphoid tissues, uptake was highest in spleen (10.9, IQR: 8.8–12.4) and bone marrow (2.5, IQR: 2.1–3.0). SUV max in tumor lesions ( n  = 41) at baseline was 1.9 (IQR: 1.7–2.3). In 11 patients, serial imaging was performed, three at week 6, seven at week 2, and one at week 4. Median [ 18 F]FB-IL2 tumor uptake decreased from 1.8 (IQR: 1.7–2.1) at baseline to 1.7 (IQR: 1.4–2.1) during treatment ( p  = 0.043). Changes in [ 18 F]FB-IL2 tumor uptake did not correlate with response. IL-2R expression in four archival tumor tissues was low and did not correlate with baseline [ 18 F]FB-IL2 uptake. No [ 18 F]FB-IL2-related side effects occurred. Conclusion PET imaging of the IL-2R, using [ 18 F]FB-IL2, is safe and feasible. In this small patient group, serial [ 18 F]FB-IL2-PET imaging did not detect a treatment-related immune response. Trial registration Clinicaltrials.gov : NCT02922283; EudraCT: 2014-003387.20